We have synthesized a series of luteinizing hormone releasing hormone (LHRH) analogs containing 15N-enriched amino acid residues in positions 5, 6, and 10. Through studying the effect of solvents (dimethylsulfoxide, water, trifluoroethanol) on 15N-chemical shifts, we have obtained information concerning the involvement of these residues in intramolecular H-bonding or interaction with solvent molecules. Continued 15N and T1 nmr studies of LHRH analogs will allow us to confirm the trends already established in the effect of solvents on chemical shifts, and provide insight into the backbone flexibility of these molecules. We have also completed the synthesis of enkephalin analogs containing 15N-enriched glycine at positions 2 and 3. The 15N and T1 nmr studies of these analogs are being carried out as described for LHRH. The concept of partial retro-inverso modification of linear peptide hormones, which was developed in our laboratory has been applied to a variety of hormones such as LHRH, the enkephalins, and thyrotropin releasing hormone (TRH). Published data on the mechanism of biodegradation of these peptides has served as a guide to the residues or segments of the molecule at which the modification should be introduced. Biological activity results of the retro-inverso modified enkephalins suggest that analogs designed according to this conceptual approach may indeed be more potent and longer acting. This approach will be extended to the synthesis of other LHRH and TRH retro-inverso analogs and also to somatostatin analogs. The biological activity and metabolism of these analogs will be studied.